Endogenous BDNF in the dorsolateral striatum gates alcohol drinking

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Brain-derived neurotrophic factor (BDNF) is implicated in addiction-related behaviors.
• Previous studies show BDNF-haplodeficient mice have altered responses to ethanol.
• Ethanol consumption increases BDNF expression in the dorsal striatum (DS).

Purpose of the Study:

• To investigate the role of BDNF within the dorsal striatum (DS) in regulating ethanol self-administration in rats.
• To determine if BDNF in specific subregions of the DS (dorsolateral striatum - DLS, dorsomedial striatum - DMS) differentially affects ethanol intake.

Main Methods:

• Rats were trained to self-administer a 10% ethanol solution.
• BDNF expression levels were measured in the DLS and DMS after ethanol self-administration.
• Viral-mediated siRNA was used to downregulate endogenous BDNF in the DLS and DMS.
• Exogenous BDNF was infused into the DLS and DMS before self-administration sessions.
• Ethanol and sucrose intake were measured.

Main Results:

• Ethanol self-administration increased BDNF expression in the DLS more than in the DMS.
• Downregulation of BDNF in the DLS, but not DMS, increased ethanol self-administration.
• Infusion of exogenous BDNF attenuated ethanol intake in both DLS and DMS.
• BDNF infusion into the DLS, but not DMS, led to early termination of drinking episodes.
• BDNF's effect on intake was specific to ethanol in the DLS, while it reduced sucrose intake in the DMS.

Conclusions:

• The BDNF pathway in the dorsolateral striatum (DLS) is a critical regulator of ethanol self-administration levels.
• Endogenous BDNF signaling in the DLS plays a key role in controlling ethanol intake.
• BDNF in different dorsal striatum subregions (DLS vs. DMS) has distinct roles in regulating ethanol and sucrose consumption.